A novel personalized vaccine for kidney cancer has demonstrated encouraging results in a Phase I clinical trial. The vaccine, designed to prevent recurrence in high-risk patients, elicited a robust immune response in all nine participants, who have remained cancer-free for a median of 34 months since receiving the vaccine. This breakthrough suggests that personalized cancer vaccines may have broader applications than previously anticipated.
Traditional vaccines protect against infectious diseases. While some, like the HPV vaccine, prevent cancer-causing infections, cancer vaccines typically treat existing cancer or prevent recurrence. Although current cancer vaccines have shown limited success, scientists are developing innovative approaches, including neoantigen vaccines, to enhance the body’s anti-cancer immunity.
“Neoantigen vaccines are personalized cancer treatments that train the immune system to recognize and attack cancer cells,” explained Dr. Toni Choueiri, a medical oncologist at Dana-Farber Cancer Institute and the senior study researcher, in an email to MaagX. “They work by introducing a patient’s unique tumor proteins (neoantigens) into the body, triggering the immune system to identify and attack them.”
Developed by researchers at Dana-Farber and the Broad Institute of MIT and Harvard, the vaccine targets advanced kidney cancers that have spread. The Phase I trial enrolled nine patients with stage III or IV clear cell renal cell carcinoma. All participants underwent surgical tumor removal, and some also received pembrolizumab, an immunotherapy drug.
The vaccines were personalized for each patient. Researchers identified neoantigens within each individual’s tumor most likely to trigger an immune response, manufactured these neoantigens, and incorporated them into the vaccine. The results have been remarkably positive.
“We found neoantigen-targeting vaccines in kidney cancer are highly immunogenic, capable of targeting key driver mutations (such as VHL) and inducing anti-tumor immunity,” stated Dr. Choueiri, also the director of the Lank Center for Genitourinary Oncology at Dana-Farber. “We observed a rapid, substantial, and durable expansion of new T cell clones specifically related to the vaccine.”
Published in Nature, the findings are significant for another reason. The research initially focused on developing a neoantigen vaccine for melanoma, a skin cancer with a high mutation burden. Kidney cancer, conversely, has a low mutation burden, raising concerns about the approach’s efficacy. However, the trial results demonstrate that neoantigen vaccines can be effective even against cancers with low mutation burdens.
While Phase I trials primarily assess safety and tolerability, the fact that all nine patients remain cancer-free after a median of 34 months (the study’s cut-off date) is highly promising. Further research with larger cohorts is needed to confirm the vaccine’s long-term efficacy.
The research team is already progressing to the next phase of research. “An ongoing multicenter international randomized study is evaluating a similar personalized neoantigen vaccine in combination with pembrolizumab,” Dr. Choueiri confirmed. “The study is currently enrolling patients who have undergone surgery for kidney cancer but remain at high risk of recurrence.”
https://dx.doi.org/10.1038/s41586-024-08507-5
https://clinicaltrials.gov/study/NCT06307431
https://www.cancerresearch.org/treatment-types/cancer-vaccines
